FRAXA Research Foundation was founded in 1994 to fund biomedical research aimed at finding a cure for Fragile X syndrome and, ultimately, autism. We prioritize translational research with the potential to lead to improved treatments for Fragile X in the near term. Our early efforts involved supporting a great deal of basic neuroscience to understand the cause of Fragile X. By 1996, these efforts had already begun to yield results useful for drug repurposing. To date, FRAXA has funded well over $25 million in research, with over $3 million of that for repurposing existing drugs for Fragile X. Here are some examples of FRAXA-funded work on repurposing available drugs for Fragile X syndrome: Lithium In the mid-1990s, the Greenough lab at the University of Illinois discovered that FMRP, the protein missing in Fragile X, is rapidly translated in dendrites in response to stimulation of glutamate receptors. FRAXA funded preclinical validation of this discovery in theRead more
With a $90,000 grant from FRAXA Research Foundation over 2017-2018, Dr. Frank Kooy at the University of Antwerp, Belgium, is investigating whether phosphorylation abnormalities are a suitable biomarker for the Fragile X syndrome. $90,000 Grant Drs. Anke Van Dijck (FRAXA fellow, ganaxolone clinical trial), Ilse van der Werf, Geert Vandeweyer, Elisa Cappuyns (FRAXA fellow, this study), Frank Kooy R. Frank Kooy, PhD Principal Investigator University of Antwerp 2018 FRAXA Research Grant $90,000 over 2 Years “This Is Your Brain on Drugs” was a large-scale US anti-drugs TV campaign promoted by Partnership for a Drug-Free America in 1987. The purpose was to discourage use of illegal drugs by showing an egg frying in a pan simulating what drugs can due to your brain. It was incredibly simple and effective. TV Guide named it one of the top 100 commercials of all time. University of Antwerp researcher Frank Kooy, PhD, has a completely different updateRead more
Our sons with Fragile X Syndrome typically go to bed early and rise early. Sometimes they jump on us while we are sleeping at 3 a.m., excited to start their day. For heaven’s sake, whY, wHY, WHY? The answer may come from Carolyn Beebe Smith, PhD, senior investigator, Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland. She is studying why children, in particularly boys, with FXS have problems sleeping. “We know sleep is important for many aspects of brain function,” said Dr. Smith, who received a PhD from the University of London where she studied the chemical pathology of Alzheimer’s for which she was awarded the Queen Square Prize. “In studies of healthy mice, we have shown restricted sleep during brain development can result in long-lasting changes in behavior. We are interested in understanding if sleep problems contribute to severity ofRead more
Massachusetts Institute of Technology Researcher Mark Bear, PhD, Sees Success Developing Disease-Modifying Treatments for Fragile X Syndrome and Other Developmental Brain Disorders Finally, hope. And it comes from the lab of Mark Bear, PhD, Picower Professor of Neuroscience, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology Dr. Bear is building on the “mGluR theory” and applied insights gained by the study of Fragile X and other genetically defined causes of intellectual disability and autism with some success. His goal is to discover and facilitate the development of disease-modifying treatments for Fragile X and other developmental brain disorders. “Neurons in the brain communicate with each other at specialized junctions called synapses,” said Bear, who earned a BS from Duke University and a PhD in neurobiology at Brown University. “Such modifications are the basis for memory storage in the brain, and go awryRead more
With $366,100 in grants from FRAXA Research Foundation, these investigators at the University of Orleans studied sensory abnormalities in Fragile X mice and test the ability of a class of drugs, BK channel openers, to rescue these abnormalities.
Sensory Overload Ever wonder why your child with Fragile X suddenly screams for no apparent reason or jumps and flaps uncontrollably seemingly for hours? You got it: hyperexcitability. But what exactly causes it? And what can fix it? Kimberly Huber, PhD, is working long and hard in her lab to answer those questions. Dr. Huber, professor, Neuroscience, UT Southwestern Medical Center, is seeking to understand how FMRP regulates connections between brain cells, called synapses, and the function of brain circuits, which are several connected brain cells. Her current focus is the study of synapses and brain circuits in the mouse that mediate sensory perception, including perception of touch and sound. She aims to understand the cellular and molecular mechanisms by which loss of FMRP causes hyperexcitable sensory circuits. The goal: to develop targeted therapeutics that can restore normal brain function and reduce sensory hypersensitivity. “Sensory brain circuits are overactive, or hyperexcitable,Read more
bio·mark·er, noun, a distinctive biological or biologically derived indicator of a process, event, or condition. Doesn’t help? Well, it’s perfectly clear to Argentinian researchers Patricia Cogram, PhD, and Paulina Carullo, MD, from the FLENI Institute in Buenos Aires, Argentina. They understand there is an urgent need for validated biomarkers after recent Fragile X syndrome clinical trials have failed on their primary endpoints. “Biomarkers are key to learning more about their correlation with clinical and behavioral characteristics across diverse developmental stages in Fragile X syndrome,” said Dr. Cogram, the principal investigator of FRAXA’s Drug Validation Initiative (FRAXA-DVI) to test preclinicaly potential compounds for FXS. “We are searching for biomarkers that could potentially be used for clinical trials for treatment in children, teenagers, and adults with Fragile X.” Cue parents. Yes, you. Targets: your Child’s Cognitive, Behavioral and Emotional Impairments Dr. Cogram and Dr. Carullo are looking for families of children withRead more
Dr. Maurin and Dr. Bardoni were awarded $90,000 over two years from FRAXA Research Foundation for their project, “Modulating cAMP And cGMP Levels As A New Therapeutic Approach For FXS”, in May 2016. They aim to gain a better understanding of how the brain develops and functions Like snowflakes, people with Fragile X Syndrome are not all alike. Some respond differently to the same drugs, as previous Fragile X research has shown. Understanding this phenomena is leading French scientists Barbara Bardoni, PhD, and Thomas Maurin, PhD, to identify new drugs to improve treatments in patients with Fragile X. Among the proteins they have identified, some are known to control brain function and development. This has helped identify a set of candidate proteins for which there are pre-existing active chemical compounds that target their activity. Using these compounds in vitro may revert some FXS hallmarks. “Access to different drugs will allow some flexibility inRead more
The University of Texas at Austin Researchers Daniel Johnston, PhD, and Jennifer J. Siegel, PhD, Explore Harnessing Nature to Improve Memory in Fragile X Mice We all forget things at times. How many times have you misplaced your car keys or forgotten the name of a person you just met? Now think how you would feel if your memory was stunted from birth? Researchers at The University of Texas at Austin know that people with Fragile X syndrome have working memory deficits because of a dysfunction with the front part of their brain. What they recently discovered is how a network of neurons is able to, on occasion, compensate for the loss of FMRP (Fragile X mental retardation protein) to regain memory function. A Different Approach “We are taking a slightly different approach to treating and potentially curing Fragile X,” said Johnston, professor, Department of Neuroscience, College of Natural Sciences,Read more
A potential new treatment for Fragile X syndrome is showing promise. While still early in development, the investigational drug was able to improve intellectual, learning and hyperactivity measures in a mouse model of Fragile X syndrome. Anavex 2-73 is a sigma-1 receptor agonist being developed for autism spectrum disorders, including Rett syndrome and Fragile X syndrome, and for Alzheimer’s disease. Anavex Life Sciences presented the data at the Gordon Research Conference for Fragile X and Autism-Related Disorders, held June 5-10, 2016 in Mount Snow, VT. The study was sponsored by FRAXA, via the FRAXA Drug Validation Initiative, and performed by Fraunhofer Chile Research, in Santiago, Chile. “The ANAVEX 2-73 data in an array of behavioral paradigms in a validated mouse model of Fragile X is very encouraging. The results are promising for both Fragile X syndrome and Autism Spectrum Disorders, since there is an overlap in the clinical as well asRead more
University of Wisconsin senior scientist Cara Westmark, PhD, studies the effect of promising therapeutics on sleep in Fragile X mice Your child finally falls asleep. You quickly celebrate before quietly turning to your favorite book or another episode of Game of Thrones. You tiptoe to bed. Exhausted, you slowly fall asleep. Enter deep REM. Minutes later, you are awoken loudly. Your bundle of joy with Fragile X syndrome (FXS) is now bouncing off you, wide awake, screaming, smiling, and demanding you join the party before you all return to bed after a few rounds of cajoling and pleading. Minutes later, repeat, rinse. Hitting home? The oh-my-it’s-way-too-early morning parties may be over if new research by Cara Westmark, PhD, is successful. Westmark, senior scientist, Department of Neurology, University of Wisconsin previously found proteins involved in Alzheimer’s disease are over expressed in Fragile X mice. She believes drug treatments that normalize theRead more
Jean-Francois Lepage, PhD, and Francois Corbin, MD, PhD, with MRI machine If all the science world’s a stage, Fragile X researchers are more than merely players. They are center stage. So believes Francois Corbin, MD, PhD, professor, Université de Sherbrooke, Canada, who directs the university’s Fragile X Clinic. Corbin, who has received more than $100,000 in FRAXA support since 2012, is leading a pilot randomized Phase II trial, exploring the tolerability and the synergistic effect of a combined therapy. They will combine minocycline, which is often used to treat acne, and lovastatin, which is used to lower cholesterol. Both drugs target specific alterations in the brain of Fragile X patients that would potentially have a combined powerful effect on their behavior. “To my knowledge, this is the first time we have a clinical trial with two different drugs combined to act on two different targets,” Corbin said. “The combined actionRead more
Sean McBride, MD, PhD, and Thomas Jongens, PhD, of the University of Pennsylvania Adapted from press release by University of Pennsylvania A new FRAXA-funded study shows how the hormone insulin – usually associated with diabetes — is involved in the daily activity patterns and learning deficits in the fruit fly model of Fragile X Syndrome (FXS). The study also reveal a metabolic pathway that can be targeted by new and already approved drugs to treat Fragile X patients, notably metformin. The scientists study the common fruitfly, Drosophila, whose genome contains a cousin, or homologue, of the human FMR1 gene called dfmr1. The lab of Thomas Jongens, PhD, an associate professor of Genetics, along with doctoral student Rachel Monyak and Sean McBride, MD, PhD, a psychiatrist at the Adult Developmental Disorders and Monogenic Disorders Clinic with Penn Behavioral Health, have been working with the fly model to find new therapies to treat the behavioralRead more
With a $110,050 grant from FRAXA Research Foundation from 2005-2016, Dr. Sumantra Chattarji at the National Center for Biological Sciences researched how the amygdala is affected by Fragile X syndrome. Results published.
2016 Funding Priorities Start with Clinical Trials While FRAXA Research Foundation’s research goals remain largely unchanged, the landscape in which we operate has changed significantly in the past few years. Negative results from the major clinical trials of investigational agents have resulted in cessation of development of mGluR5 antagonists for Fragile X syndrome. There is still much evidence that this drug class could be successful as a Fragile X therapeutic, but we do not see the need for more “proof of principle”-type preclinical research on mGluR5 antagonists. Studies of possible mechanisms of tolerance in Fragile X would be appealing as a topic going forward, as would studies of circuit function in Fragile X, since available evidence suggests some form of circuit-based (rather than synaptic) tolerance in Fragile X mice and humans. Other potential areas of interest would include exploration of combination treatment strategies, both in animal models and in clinicalRead more
Claudia Bagni, PhD, an author of the new study published in Neuron and a previous recipient of a FRAXA research grant Researchers Investigate Treatment Targets Which May Address Both Fragile X Syndrome and Alzheimer’s Disease Last week researchers at VIB Leuven in Belgium published evidence that a brain pathway involving the protein APP (Amyloid Precursor Protein) plays a vital role in development of Fragile X syndrome, one of the most common causes of autism. Scientists led by Dr. Emanuela Pasciuto in the laboratory of Prof Claudia Bagni published findings of their study in the journal Neuron. The team identified the molecular mechanisms behind the elevated levels and metabolism of APP protein in a mouse model. This dysregulation affects brain development and behavior, at a stage where the infant’s neuronal connections i.e. synapses are being formed and remodeled. Using a newly developed agent the team was able to reduce the cellular dysfunctionRead more
Boston Bruins Foundation’s $90,000 commitment to FRAXA Bruins Foundation Executive Director Bob Sweeney pledging a $90,000 donation to FRAXA Research today at Shared Living Collaborative’s Gateway Farm in Merrimac, MA. The award will enable the organization to fund an entirely new research project aimed at developing new treatments for Fragile X, a genetic syndrome that is the most common inherited cause of autism. #NHLBruins A photo posted by Boston Bruins (@nhlbruins) on May 28, 2015 at 10:29am PDT The new fellowship to be funded by this award goes to Drs. Lynne Maquat and Tatsuaki Kurosaki of the University of Rochester. They will investigate nonsense-mediated mRNA decay (NMD) in Fragile X. NMD is a “housekeeping” process that cells use to prevent faulty proteins from being made. But there is too much of it in Fragile X syndrome. There are already available drugs that suppress NMD – including caffeine -- and so If this projectRead more
CANDO Team, left to right: Mary Beth Kadlec, Program Director, Occupational Therapist; David Cochran, Assistant Medical Director,Child Psychiatrist; Jean Frazier, Medical Director, Child Psychiatrist; Susan Swanson, Speech and Language Pathologist. (Not pictured: Van Silka, Adult Psychiatrist; Mary Crane, Board Certified Behavior Analyst;and Kelly Hurley, Autism Resource Specialist). Fragile X Programs aimed at improving the lives of individuals with Fragile X Syndrome at UMASS Medical School (UMMS) and UMASS Memorial Health Care (UMMHC) 1. Fragile X Syndrome Behavioral Health Clinic The Center for Autism and Neurodevelopmental Disorders (CANDO) is opening a specialty clinic for individuals with Fragile X Syndrome (under the direction of Dr. Jean Frazier) to evaluate and provide treatment for behavioral challenges. If you have questions about our program and/or have a need for our new clinical service, please call CANDO at 774-442-2263. 2. Expanded Fragile X Clinical Research The Child and Adolescent Neurodevelopment Initiative (CANDI, with Co-Directors Drs. Frazier and Kennedy) has two active studies aimed at expanding our knowledge about how toRead more
With a $349,000 grant from FRAXA Research Foundation from 2008-2015, Dr. Paul Lombroso and his team at Yale University researched if inhibiting STEP could reduce behavioral abnormalities in Fragile X syndrome. Results published.
Scientists have found increases in the numbers of neurons in brain regions of autistic children, suggesting a problem in developmental programmed cell death pathways. One of the most important effectors of neuronal survival during brain development is the “anti-cell death” protein Bcl-xL. While the normal function of Bcl-xL is to maintain a healthy number of neurons and synapses, over-expressed Bcl-xL can cause an overabundance of synaptic connections. This may be happening in Fragile X.
With a $90,000 grant from the FRAXA Research Foundation, Dr. Robert Wong is investigating how seizures are generated in Fragile X neurons. More generally, he is looking at how synapses are modified to enable learning and memory and how this process is impaired in Fragile X. $90,000 Grant Robert Wong, PhD Principal Investigator State University of New York 2013-2014 FRAXA Research Grant $90,000 over 2 Years Abnormal increases in sensitivity of a type of glutamate receptor (group I mGluR) cause brain malfunction, including epilepsy, in Fragile X syndrome (FXS). We are examining a newly uncovered regulation of this increased group I mGluR sensitivity by a second type of glutamate receptor, the NMDA receptor. By looking at audiogenic seizures in FXS model mice, NMDA receptor blockers were found to robustly suppress these seizures at the young developmental stage. In contrast, the same antagonists activated seizure activities, normally dormant, in adult FXS model mice and in a CGGRead more
Researchers led by Dr. Karen O’Malley at Washington University School of Medicine in St. Louis have published results of their work on mGluR5 and Fragile X syndrome. FRAXA Research Foundation provided funding for this work from 2009 until 2013. Pharmaceutical companies have developed therapeutic compounds to decrease signaling associated with the mGlu5 receptor, moderating its effects on brain cells’ volume knobs. But the compounds were designed to target mGlu5 surface receptors. In light of the new findings, the scientists question if those drugs will reach the receptors inside cells. “Our results suggest that to have the greatest therapeutic benefit, we may need to make sure we’re blocking all of this type of receptor, both inside and on the surface of the cell.” “This should be a factor we consider when we design drugs to target brain cell receptors. Do we want to reach cell surface receptors, receptors inside the cell
Finding May Explain Many Brain Disorders, Lead to Prevention and Treatment adapted from Weill Cornell Medical College press release A new study led by Weill Cornell Medical College scientists shows that Fragile X syndrome occurs because of a mechanism that shuts off the gene associated with the disease. The findings, published today in Science, also show that a compound that blocks this silencing mechanism can prevent Fragile X syndrome – suggesting a similar therapy may be possible for 20 other diseases that range from mental retardation to multisystem failure. While researchers have known for more than two decades that the culprit behind Fragile X is an unusual mutation characterized by the excess repetition of a particular segment of the genetic code, they weren’t sure why the presence of a large number of these repetitions – 200 or more – sets the disease process in motion. Using stem cells from donated human embryos thatRead more
Nice writeup on SFARI.org – Simons Foundation Autism Research Initiative – about Dr. Richard Jope’s research. Dr. Jope won the 2013 FRAXA Pioneer Award for this work. The mood stabilizer lithium and two other drugs that block an enzyme called GSK-3 reverse cognitive deficits in a mouse model of Fragile X. Molecular mechanisms: Enzyme blockers help Fragile X mice — SFARI.org – Simons Foundation Autism Research Initiative
Complete Phase II/III Clinical Trials of mGluR5 Antagonists – and learn results Currently two large pharmaceutical companies – Novartis and Roche – are conducting large-scale clinical trials of experimental new medications for Fragile X syndrome which target the mGluR5 pathway. The Novartis trial has finished enrolling adults and adolescents, while a pediatric trial is set to begin soon. The Roche trial is well on the way to completion as well, but is still enrolling some age groups. FRAXA has been working diligently to educate families about these trials in the hopes of getting them completed as quickly as possible. Our goal (of course) is to discover whether these new drugs could be effective treatments for Fragile X, and to see these trials through to marketing of mGluR5 antagonists for Fragile X. Accelerate Clinical Trials of Investigational Treatments, based on research already funded by FRAXA New treatment strategies have emerged and